The nemesis of solid tumors?

May 27, 2022/eMedClub News/--With the great success of CAR-T commercialization, the cell therapy track has become one of the hottest tracks at the mome.
Driven by the huge demand for tumor medical care, TCR -T cell therapy has arrived as schedul.
TCR-T cell therapy has shown unprecedented potential in the treatment of solid tumo.
With its advantage of targeting multiple antigens in tumors, it has attracted more and more industry gian.
The clinical efficacy of TCR-T cell therapy in solid tumors remains challenging, in part due to suboptimal T cell persistence and activation in vivo and the potential for tumor antigen esca.
Recent studies by Elicio Therapeutics have shown that the combination of TCR-T cell therapy and lymph node-targeted AMP vaccine can overcome these challenges and improve the therapeutic effect of TCR-T cell therapy on solid tumo.
▲ Image source: Elicio Therapeutics official website AMP vaccine is a new vaccine developed by Elicio Therapeuti.
After AMP vaccination, homologous peptides and adjuvants can be delivered to lymph nodes, thereby inducing dendritic cell activation and promoting tumor-specific TCR-T In vivo activation of cells to enhance the antitumor efficacy of adoptively transferred cel.
Elicio Therapeutics is a clinical-stage biotechnology company developing a series of novel immunotherapies for the treatment of cancer and other diseas.
Recently, Elicio Therapeutics published data on bioRxiv showing the combination of AMP vaccine and TCR.
Robust efficacy: AMP vaccination significantly enhanced the antitumor response of TCR-T cells, while also inducing epitope spread among endogenous T-cell populations, resulting in solid tumor persistence in established syngeneic tumor models Cures; the combination of vaccine and TCR-T cell therapy enhances the in vivo viability of adoptively transferred TCR-T cells and promotes in situ priming of endogenous antitumor T cell pools, thereby enhancing the antitumor efficacy of adoptively transferred cells; in Inoculation of AMP-mKRAS peptide in transgenic mice can significantly enhance the activation, persistence and specific target lysis of mouse KRAS-specific TCR-T cells; AMP vaccine and clinically relevant peptides (NY-ESO-1, mKRAS, HPV16 E7) The matching showed the clinical potential of AMP vaccination in enhancing human TCR-T cell proliferation, activation and antitum.
Off-target and safety concerns in TCR gene transfer The optimal target antigens for T cell therapy are those present only in tumor cells and not in healthy cells; however, in most cases the tumor target antigens of choice are either overexpressed or Abnormally expressed proteins may exist to varying degrees in normal cel.
Thus, genetically engineered T-cell therapy can also elicit potent cellular immune responses against normal cells, even cells expressing target antigens at low leve.
This type of toxicity is known as "off-target effects" because engineered T cells cannot distinguish between normal and cancer cells expressing the target antig.
In addition, the ACT of TCR-T cells showed high tumor killing, but some serious adverse events were also seen in some clinical studi.
Optimizing TCR affinity in engineered T cells is critical, and receptor affinity can determine the safety and efficacy of T cell thera.
In terms of efficacy, affinity TCR interactions are sufficient to activate T cells, but strong affinity is required to maintain T cell expansi.

In Phase I/II ACT clinical trials, low-affinity engineered T cells showed safer properties, but their antitumor responses were weak.

By recognizing the TCR-pMHC interaction of T cells, engineered T cells can be divided into high-affinity and low-affinity typ.

Although HSV-TK has shown safety in cell-based immunotherapy, introduction of phosphorylated nucleoside analogs is requir.

Another safer inducible T cell safety switch is called inducible caspase-9 (iC
iC9 is a modified human FK-binding protein that is activated by the small molecule compound AP1903, a process dependent on the mitochondrial apoptotic pathw.

The iC9 suicide gene was less immunogenic and elicited a reduced immune response against the transgenic cel.

An iC9-based safety switch has been shown to have more potential for cell therapy than previous suicide gen.

Recent progress of TCR-T cell therapy According to the Cortellis database, as of May 2022, there are 117 drugs in the preclinical and above research stages worldwide, including 61 preclinical, 30 clinical phase 1, and 23 clinical phase More than 70% of the global TCR-T projects under development are solid tumors, mainly including metastatic non-small cell lung cancer, hepatocellular carcinoma, multiple myeloma, soft tissue sarcoma, head and neck cancer, melanoma, liposarcoma and cervical cancer cancere.

In terms of targets, cancer-testis (CT) antigen is still a hot spot in research and development, and the number of projects targeting NY-ESO-1 is at the forefro.

On September 13, 2021, Adaptimmune announced that it will disclose Phase 1 safety clinical data of its TCR-T therapy ADP-A2M4CD8 at the 2021 ESMO Annual Meeti.

It will continue to evaluate its efficacy and safety in the Phase 2 clinical SURPASS 2 study for esophageal cancer and gastroesophageal junction adenocarcino.

Recommended reading: From $1 to $11, the positive data of TCR-T in the treatment of solid tumors has made Adaptimmune tenfold in value within six monthsYimai Meng broke the news A*02:01/NY-ESO-1 TCR-T Cell Injection" was accepted by the China National Medical Products Administration Center for Evaluation (CD.

Recommended reading: Another solid tumor TCR therapy IND approved; CAR-T and TCR-T compete for more solid tumor territory April 19, 2022, according to the official website of the Center for Drug Evaluation (CDE) of the State Food and Drug Administration - Clinical Trials Announcement of implied license, Xiangxue Life Science Technology (Guangdong) .

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"TAEST1901 injection" clinical trial application (IND) was approved (acceptance number: CXSL2200058), the indication is: the genotype to be used for the treatment of HLA-A*02 :01, advanced hepatocellular carcinoma or other advanced tumors with positive expression of tumor antigen A.

This is another IND approved by Xiangxue Precision after TAEST16001 injecti.

Recommended reading: Another solid tumor TCR therapy IND approved; CAR-T and TCR-T compete for more solid tumor territory Summary TCR-T cell therapy is an exciting and fast-growing emerging field, and its use opens A new approach to the treatment of cancer, viral infections and other immunomodulatory diseases has been develop.

Clinical studies have demonstrated varying degrees of feasibility, safety, and efficacy using TCR-T for the treatment of cancer and viral infectio.

So far, TCR-T cell immunotherapy has achieved good results in the treatment of some solid tumors, especially for liver cancer, melanoma, and synovial cell sarco.

The efficacy of other solid tumors such as myeloma remains to be further clinically verifi.

In order for TCR-T to reach its full potential, the manufacture of cell therapies requires significant innovation, one of the biggest obstacles to the technology becoming mainstre.

But we believe that with technological innovation and continuous accumulation of experience, TCR-T cell therapy will become a "sharp edge" in the treatment of canc.

References:https:// -cell-therapy-enhances-anti-tumor-function-and-eradicates-solid-tumors/https:// & Zhang,.

T cell receptor-engineered T cells for cancer therapy: current status and future directio.

Protein Cell 9, 254–266 (201
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org/11007/s13238-016-0367-1——List of recent popular activities——▼On June 1st, thinking on the release criteria of gene therapy--Gene editing off-target detection and verification